Fungicides have myriad uses, including for crop protection; as food, feed, and cosmetics preservatives; and as therapeutic agents for both human and veterinary applications. Crop yield reduction, foodborne diseases and fungal infections of both humans and animals are a problem in both developed and developing countries.
Non-ribosomal peptides, including cyclic amphiphilic lipopeptides such as surfactins, iturins and fengycins, are well-recognized for their antimicrobial properties and have been used in the field of crop protection. Because of their mode of action, they also have potential uses in biopharmaceutical and other biotechnology applications. Lipopeptides may be obtained through fermentation of various soil bacteria, including Bacillus subtilis and Bacillus amyloliquefaciens. Lipopeptides kill fungi by disrupting cell membranes. The potential for the development of fungal resistance to these compounds is expected to be very low since they act directly upon membrane lipids and not on a single site protein target. Further, lipopeptides are of low risk to workers and consumers; in fact, crops treated with Bacillus-based products may be harvested on the day of treatment.
Due to their hydrophobic nature, the lipopeptides produced by Bacillus subtilis and Bacillus amyloliquefaciens may have limited bioavailability when applied to plants, plant parts, or soil. Compounds that enhance the bioavailability of these lipopeptides could increase their antifungal activity. As shown below in Examples 28 and 29, an enhanced ability to disperse in an aqueous supernatant rather than to remain in a cell pellet may indicate increased lipopeptide bioavailability (see FIG. 5 and FIG. 6).
There is a need for improved formulations of lipopeptide-producing strains of Bacillus subtilis and Bacillus amyloliquefaciens with increased antifungal activity. Improvements to the efficacy of Bacillus-based products, especially those that are not susceptible to development of fungal resistance, are highly desirable. There exists a continuing need in the art for such improvements to Bacillus-based fungicidal formulations.